The present invention relates generally to materials analysis and, more particularly, to systems and methods which use fluorescence to analyze mixtures.
Many areas of materials processing involve mixing several components to form a final product. The uniformity of the mixture and concentration of particular components may both be critical to the quality of the final product, for example, in the preparation of pharmaceuticals. Many pharmaceutical processes, for example, employ analytical steps to assess the uniformity of the mixture and/or the concentration of a component, such as the active drug ingredient. Such steps may be used during process development efforts to optimize process variables or during commercial manufacturing processes, for example, as a quality control measure.
One conventional method for analyzing mixtures during processing involves physically removing a sample from the mixture and determining its composition by any number of analytical techniques known in the art. Generally, these methods may be susceptible to sampling and processing errors. For example, the composition of the sample may not be indicative of the actual mixture and it may be difficult to maintain consistent sampling procedures. The accuracy of the compositional measurements, therefore, may be compromised. In addition, the sampling procedure is invasive and, thus, disrupts the process. Furthermore, the methods can be time consuming and cumbersome to execute.
Another method for analyzing a mixture during processing involves using near infrared (NR) spectral analysis. Such a method has been disclosed, for example, in Aldridge, U.S. Pat. No. 5,946,088. This method generally is used to analyze the homogeneity and potency of a mixture on-line. However, because the method employs NIR spectral analysis, it may be limited in its sensitivity, specificity for the types of materials which can be analyzed, and its speed of analysis.
Accordingly, a need exists for an improved technique for analyzing mixtures during processing.
The invention provides systems and methods for analyzing mixtures and, particularly, for analyzing mixtures during processing. The methods and systems utilize fluorescence to non-invasively analyze one or more components of the mixture. The analysis may provide a variety of compositional information such as the chemical identity of components, the concentration of components, the uniformity of the mixture and other information. A number of different types of processing equipment can be configured to provide the analysis and, accordingly, the analysis may be performed during a number of processing operations. The system and methods are particularly useful in processing mixtures which are preferably homogeneous blends, such as pharmaceutical products.
In one aspect, the invention provides a method of processing materials. The method includes measuring the uniformity of a mixture of more than one component using fluorescence during processing of the mixture.
In another aspect, the invention provides a method of processing materials. The method includes non-invasively analyzing a mixture of more than one component using fluorescence during processing of the mixture.
In another aspect, the invention provides a method of processing materials. The method includes measuring the concentration of a component of a mixture using fluorescence during processing of the mixture.
In another aspect, the invention provides a method of materials analysis. The method includes measuring the concentration of at least one solid component of a mixture using fluorescence.
In another aspect, the invention provides a method of processing materials. The method includes measuring the stability of a mixture of more than one component of a mixture using fluorescence during processing of the mixture.
In another aspect, the invention provides a method of materials analysis. The method includes processing a mixture of more than one component in a processing apparatus, transferring the mixture from the processing apparatus, and measuring the concentration of a component of the mixture remaining in the processing apparatus, after transferring the mixture, using fluorescence.
In another aspect, the invention provides a system for processing materials. The system includes a processing apparatus configured to process a mixture of more than one component. The system further includes a fluorescence instrument operatively associated with the processing apparatus capable of measuring the uniformity of the mixture during processing of the mixture.
In another aspect, the invention provides a system for processing materials. The system includes a processing apparatus configured to process a mixture of more than one component. The system further includes a 1 fluorescence instrument operatively associated with the processing apparatus capable of non-invasively analyzing the mixture using fluorescence during processing of the mixture.
In another aspect, a system for processing materials is provided. The system includes a processing apparatus configured to process a mixture of more than one component. The system further includes a fluorescence instrument operatively associated with the processing apparatus capable of measuring the concentration of one component of the mixture during processing of the mixture.
Among other advantages, the invention provides systems and methods for non-invasively measuring the uniformity and/or the concentration of a component during processing. As a result, the process is not disturbed by the analysis and is, generally, not susceptible to the sampling and measurement errors associated with conventional invasive methods of analysis. Furthermore, the analysis may be conducted on-line and in real-time to provide compositional information during the process. This permits adjustment of processing variables to optimize the process.
LIF analysis also provides a strong signal which may result in a higher sensitivity and specificity than achievable in NIR analysis. In particular, this higher sensitivity enables the systems and methods of the invention to be used to detect species at low concentrations, for example, active ingredients in certain pharmaceutical products. The higher specificity permits highly accurate identification of compounds.
Furthermore, the LIF instrument used in the systems and methods of the invention may be readily used in conjunction with any number of types of processing equipment, especially equipment used in pharmaceutical processing. Generally, the LIF instrument is small, portable, and easily be mounted on a variety of different locations on processing equipment.
Various embodiments of the present invention provide certain advantages and overcome certain drawbacks of the conventional techniques. Not all embodiments of the invention share the same advantages and those that do may not share them under all circumstances. Other advantages, novel features, in aspects of the invention will become apparent from the following detailed description of the invention when considered in conjunction with the accompanying figures, and from the claims.